Essential Molecular Biology (BIOC0007) Notes - DNA
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Course
Essential Molecular Biology (BIOC0007)
Institution
University College London (UCL)
Explore Essential Molecular Biology at UCL. Unveil the intricacies of DNA dynamics, covering damaged DNA, repair mechanisms, detection, and cutting-edge recombinant technologies. Tailored for Year 1 students, these notes offer a humanized academic guide, enriching your understanding of DNA replicat...
DNA
DNA Structure and Packaging
DNA molecule
o Genetic code
Instructions that enable us to: live + reproduce + pass information to the next generations
Identical in almost all species – number of genes varies
Gene = linear string of DNA nucleotides – contains information to produce proteins in the
cell
Packaging
o Chromatin = open DNA
o Chromosome = packaging tightly DNA
o Nucleotides
Monomer of DNA
Structure
5 carbon pentose sugar + phosphate + nitrogenous base
+ +
Base
GUArdian Angels are PURe and TWO wINGed (gUAnine and Adenine are PURines
and TWO rINGed)
Purines = 2 ringed
o Adenine – A
o Guanine – G
Pyrimidines – 1 ringed
o Cytosine – C
o Thymine – T
o Uracil – U
RNA vs DNA
DNA = deoxyribose sugar
RNA = ribose sugar
DNA = thymine
RNA = uracil
o Nucleosides vs nucleotides
Nucleoside = sugar + base
Nucleotide = sugar + base + phosphate
Glycosidic bond = base
covalently bonded to sugar
o Between C1 sugar and
N9 purine / N1
pyrimidine
Phosphate ester bond = phosphate covalently bonded to nucleoside
o Phosphate attaches to the 3’ or 5’ OH of nucleoside
,DNA
o Polynucleotide
Linear sequence of nucleotides
Backbone = sugar + phosphate
Different bases
Phosphodiester bond
Nucleotides joined by phosphodiester bond
Directionality = 5’-3’
DNA double helix 3D conformation
o Two single strands associated via covalent hydrogen and van der Waals bonds – forming double
stranded DNA (dsDNA)
o Complementary base pairing
A + T = 2 hydrogen bonds
C + G = 3 hydrogen bonds
o Chargaff’s rule = ratio of purines to pyrimidines = 1:1
o Antiparallel strands
5’ end of one strand pairs with 3’ end of other
o Complementary strands
Physical properties of double helix
o Beta form
Most energetically favourable form of DNA
Two strands wind around one another in a right-handed double helix – every 10.5bp
o Helical structure repeats every 10.5bp
Sugar phosphate backbone is hydrophilic = lies outside of the helix (periphery)
Base pairs are hydrophobic = lies inside the helix (core) – base stacking
Base stacks bind asymmetrically with the sugar phosphate backbone – forming a
major (13Å) and minor (9Å) groove
DNA conformations
o Beta-DNA
Most abundant
Right-handed
Repeat unit = 10.5bp
Helix diameter = 20A
Central core = solid
Major groove = wide and deep
Minor groove = narrow and deep
o Alpha-DNA – results from DNA dehydration
Less common
Right-handed
Repeat unit – 11bp
Helix diameter – 26A
Central core – hollow
Major groove – narrow and deep
Minor groove – wide and shallow
o Z-DNA – results from methylation, stress, and high salt concentration
Least observed
Left-handed, zig-zag pattern
Repeat unit – 12bp
Helix diameter – 18A
Central core – solid
Major groove – flat
Minor groove – narrow and deep
, DNA
DNA folding into chromatin
o Histones
Nuclear proteins responsible for compacting and organising DNA
o Chromatin
Complex of histones + DNA = ½ DNA + ½ protein
o Euchromatin
Chromatin in relatively decondensed regions stained lightly + is transcriptionally active =
euchromatin
Found during interphase – when genome is open and active
o Heterochromatin
More compacted regions stain more darkly – transcriptionally more inactive =
heterochromatin
Found in periphery of nucleus during interphase + centromeres and telomeres of
chromosomes
Nucleosome
o 4 core histones – highly conserved
H2A + H2B + H3 + H4
Rich in lysine + arginine
Carry positive charges – counteract DNAs negative
charge = stabilising DNA
Each histone contains intrinsically disordered flexible N terminus
histone tail
19-39 residues
o Extend from the nucleosome complex
o Needed for chromatin condensation (1030nm)
o Influence chromatin structure
N-terminus tails = H2A, H2B, H3, H4
C-terminus tails = H2A, H2B
o 146bp of DNA wraps around a histone complex in a left-handed manner
= forming nucleosome
Nucleosome = unit of eukaryotic chromatin
o Histone octamer
Disk-shaped protein complex at the centre of the nucleosome
Contains 2 copies of each of the 4 core histones
Two monomers of H3 and H4 = form a tetramer
Followed by association of 2x H2A-H2B heterodimers
Levels of chromatin condensation
o Linker DNA
Nucleosomes – connected by free DNA = linker DNA
o Chromatin packaging has several layers – leading to more condensed DNA
1 – 10nm fibre = nucleosome association with linker DNA
2 – 30nm fibre = H1 linker histone bound to linker DNA nucleosomes move closer to each
other (beads on a string)
H1 is removed during DNA transcription
o Further condensation to form chromosomes
30nm fibre further condensed
Large loops of chromatin in 30nm fibres – anchored to central scaffold forming
chromosome
o Summary of condensation – 30nm 300nm 700nm 1400nm metaphase chromosomes
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